The regional cerebral metabolic rate for glucose was measured with the (14C)2-deoxy-D-glucose technique in young and aged male Fischer-344 rats, following administration of cholinergic (arecoline), dopaminergic (haloperidol, bromocriptine), and serotonergic (m-chlorophenylpiperazine) drugs. For arecoline, the absence of age differences in most brain areas indicated that muscarinic receptor mechanisms are intact in the rat brain during aging. Responses to bromocriptine and haloperidol were reduced in senescent as compared to younger rats, suggesting reduced central dopaminergic function, and an imbalance between cholinergic and dopaminergic systems. Structural analogs of physostigmine, a cholinesterase inhibitor, were synthesized. Some were shown to have longer half-lives and greater selectivity for acetylcholinesterase than does physostigmine.